The proposed program is designed to develop investigators derived from 2 sources: 1) PHYSICIANS, with prior training in neurology (including pediatric neurology), pediatrics or neuropathology; and 2) PhDs, with a background in virology or molecular biology. The goal is to steer them into problems in neurological disease, which can be attacked by these disciplines. This is a laboratory research training program which includes experience with important methods in virology and molecular biology. The following disciplines are currently being used: Protein purification and nucleic acid hybridization, molecular genetics, production and characterization of cDNA libraries, DNA sequencing, molecular cloning, virology, production of monoclonal and polyclonal antibodies, cell sorting, quantitation of humoral and cell-mediated immune responses, preparation of subunit viral vaccine and its expression, and the molecular aspects of viral pathogenesis. Each trainee, in collaboration with one of 10 specific trainers, undertakes an independent study, which provides experience in the design and analysis of experiments, and in the presentation and publication of results. Weekly formal meetings and presentations provide constant interchange between trainees and frequent exposure to many trainers. Research is also often supplemented by formal courses and informal seminars. This training program builds on several strengths: 1) Well-established Graduate Faculty in Microbiology & Immunology and in Molecular Biology which grant the PhD degree; 2) an NIH funded Neuroscience Center of Excellence; 3) a contingent of investigators here and at the Eleanor Roosevelt Institute for Cancer Research with proven track records and commitment to research in neurovirology and the molecular biology of neurological disease; 4) 3 NIH-supported program project grants focused on neurological disease produced: By neurotropic virus infection, and by somatic or mitochondria DNA defects; and 5) considerable individual experience of the trainers with post-doctoral fellows as detailed in the body of this proposal. The training facilities for programs not only are extensive within the immediate surroundings of the individual trainers laboratories, but also extend to collaborating laboratories at UCHSC when necessary. The laboratories are well equipped for biochemical, molecular biological, immunological, genetic and neuroscience investigations. Upon completion, post-doctorals are qualified to begin junior faculty positions as independent investigators to study neurovirologic or molecular biologic aspects of neurologic diseases.